Adverse drug reactions to unlicensed and off‐label drugs on paediatric wards: a prospective study

Abstract

To determine the incidence of adverse drug reactions (ADRs) to unlicensed and off‐label drugs used in paediatric inpatients, we carried out prospective surveillance on five different paediatric wards in a regional children's hospital for 13 wk. Comparison of the use of each drug with its summary of product characteristics was made to determine whether the drug was used in an unlicensed or off‐label manner. The presence of an ADR was determined using previously defined criteria. In total, 4455 courses of drugs were administered to 936 patients in 1046 admissions. In 507 (48%) of the 1046 admissions, patients received one or more unlicensed or off‐label drugs. ADRs occurred in 116 (11%) of the 1046 patient admissions. ADRs were associated with 112 (3.9%) of the 2881 licensed drug prescriptions and 95 (6%) of the 1574 unlicensed or off‐label drug prescriptions. Use of drugs in an off‐label or unlicensed manner to treat children is widespread. ADRs are a significant problem following unlicensed or off‐label drug prescriptions. □Adverse drug reactions, children, off‐label, unlicensed

Off-label antibiotic use in children in three European countries

“…This means that alternative antibiotic therapies are needed, particularly for neonates who remain in NICUs for several days, and justifies the use of meropenem in some cases. Meropenem has a 21 broad antibacterial spectrum, a very good safety profile, and good pharmacokinetic and pharmacodynamic characteristics [31]. However, although it has been widely successfully used to treat severe infections, including bacterial sepsis and meningitis in children and infants aged ≥3 months [32], it has not yet been registered for neonates and infants aged <3 months.…”

“…We found that quinolones and linezolid were mainly used in children with cystic fibrosis or oncohematological diseases in which complicated infections due to bacterial resistance to commonly used antibiotics is very frequent. 21 13 The high prevalence of antibiotic prescriptions for off-label indications or at unregistered doses in our NICUs and pediatric wards is in line with previously published data concerning the pediatric use of antibiotics [1][2][3][4][5][6][7][8][9][10][11][12]. It may be that pediatricians have a poor understanding of the properties and characteristics of antibiotics nor how they should be prescribed to treat bacterial diseases at different pediatric ages, but our findings raise some interesting afterthoughts.…”

“…Off-label drug use can cause significant damage in the developing fetus or child, one of the best examples being the grey baby syndrome due to chlorampenicol [16,17]; but it also gives rise to many minor but not marginal adverse events requiring hospitalisation or additional therapies [18][19][20][21][22]. A number of health authorities have recognised the need to conduct specific studies in children in order to reduce the problem of off-label use.…”

Off-Label Prescribing in Pediatric Outpatients

“…However, administration of a drug outside the conditions assessed during clinical trials may result in adverse drug reactions (ADRs). [1][2][3] Moreover, the specificity of children's physiology and pharmacology should not be neglected. 4 For years, the lack of drug evaluation in children has been evoked as a factor favoring off-label prescribing.…”

Healthcare professional experiences and attitudes on unlicensed/off-label paediatric prescribing and paediatric clinical trials

“…[10] There is growing concern about the safety and efficacy of unlicensed/off-label medicine use in children particularly due to the lack of long-term safety and efficacy data in this vulnerable group and due to evidence suggesting an increased risk of adverse drug reactions (ADRs) and treatment failure. [11][12][13] The ethical obligation of providing the best available treatment to children coupled with a lack of availability of licensed paediatric products, highlights the need for an increased number of clinical trials in children. Performing such trials, however, requires special attention to the various challenges faced in this population.…”